Our work has focused upon studies of the protease complexed with two potent inhibitors, (a) DMP323, a member of a novel class of symmetric, specific and potent (Ki about 10-1000 pM) inhibitors in which a diol moiety is incorporated into a seven membered cyclic urea ring and (b) KNI272, an asymmetric mono-ol inhibitor having high affinity (Ki ca. 5 pM) and specificity for the protease. The asymmetry of the KNI272 inhibitor breaks the degeneracy of the protease monomer chemical shifts, and has enabled us to obtain monomer specific assignments, which have in turn allowed us to compare the internal dynamics and H/D exchange rates of backbone amides in separate monomers. Differences in monomer flexibility have been observed for three residues in the protease, and these differences in flexibility correlate with differences in structure. Molecular dynamics of a fully active, but stable protease mutant (Q7K, L33I, L63I) have also been studied and reveal that the flaps that cover the active site in the structures of the inhibited protein are highly flexible. In future work, we plan to compare the dynamics of active site side chains in the free and inhibited protein.